Mercapto-or alkylthio-substituted terpenoids

ABSTRACT

THERE ARE PROVIDED NOVEL MERCAPTO- OR ALKYLTHIO-SUBSTITUTED OXO-TERPENOIDS HAVING 10 CARBON ATOMS IN THE TERPENOID SKELETON. THESE NOVEL COMPOUNDS MAY BE ACYCLIC MONOCYCLIC OR BICYLIC. THE NOVEL COMPOUNDS ARE USEFUL AS ODORANTS PARTICULARLY, BUT ALSO FOR PRODUCING AROMAS, E.G. OF A VEGETABLE NOTE.

United. States Patent Ofice 3,819,712 MERCAPTO- OR ALKYLTHIO-SUBSTITUTED TERPENOIDS Dietmar Lamparsky, Wangen-Dubendorf and Peter Schudel, Grnt, near Wetzikon, Switzerland, assignors to Givaudan Corporation, Clifton, NJ.

No Drawing. Filed Sept. 3, 1970, Ser. No. 69,457 Claims priority, application Switzerland, Sept. 10, 1969, 13,7 /69 Int. Cl. C07c 49/44 US. Cl. 260-593 R 1 Claim ABSTRACT OF THE DISCLOSURE There are provided novel mercaptoor alkylthio-substituted oxo-terpenoids having 10 carbon atoms in the terpenoid skeleton. These novel compounds may be acyclic monocyclic or bicyclic. The novel compounds are useful as odorants particularly, but also for producing aromas, e.g. of a vegetable note.

RELATED APPLICATIONS This application claims priority from Swiss application 13,748/69 filed Sept. 10, 1969.

FIELD OF THE INVENTION Novel aromatizing agents.

SUMMARY OF THE INVENTION The present invention is concerned with new mercaptoor alkylthio-substituted terpenoids of the general formula Xm Y Ra R

Ru RI I wherein R represents hydrogen or together with R represents a CC bond,

R represents hydrogen or together with R represents a dimethylmethylene group, or, when R is isopropyl, together with R represents a CC bond,

R represents hydrogen or together with R represents a dimethylmethylene group,

R represents hydrogen or together with R represents a CC bond,

R represents hydrogen or, when R signifies isopropyl, to-

gether with R represents a CC bond,

R represents isopropyl or together with R or with R represents a dimethylmethylene group,

R represents methyl,

X represents a CC double bond taking the place of a CC single bond,

m'=0 to 2,

Y represents oxo bound to a primary or secondary C-atom and Z represents mercapto or lower alkylthio located in the (it-position to the carbonyl function,

provided that when R R and R represent hydrogen, R represents isopropyl, R together with R represents a CC bond, Y is 18 to the carbon atom bearing the substituent R", m=0, Z is a to the carbon atom bearing the substituent R and p to the carbon atom bearing the substituent R then Z represents alkylthio, their use as odorants and/or flavourings, as well as a process for their manufacture.

The above formula I includes mercaptoor alkylthiosubstituted acyclic, monocyclic or bicyclic monoterpenes each containing a carbonyl group, the mercapto or alkyl- 3,819,712 Patented June 25, 1974 thio substituent Z being located in the fi-position to the carbonyl function.

DESCRIPTION OF THE PREFERRED EMBODIMENTS Formula I, as also all other formulae appearing in the description and the claims, is meant to include all stereoisomers.

The above formula I includes the compounds of the following general formulae as sub-groups the compounds of formulae I1 and I-2 claiming particular interest.

In formulae I-l to L5, X, Y, Z and m. have the significance stated above. The compounds I-l are acyclic and have a carbon skeleton like, for example, citral or tagetenone. The compounds I-2 are monocyclic and have the p-menthane skeleton. The compounds I-3, I-4 and I5 are bicyclic and display the skeleton of pinane, thujane or carane.

By lower alkylthio in the sense of the above definition are meant alkylthio residues the alkyl portion of which is straight-chain or branched and preferably contains up to 5 C-atoms; examples of such alkyl residues are: methyl (preferred) ethyl, n-propyl, iso-propyl, n-butyl, sec. butyl, tert. butyl, amyl, etc.

The double bonds represented in the above formula I by X can be located in any position of the molecule, thus, for example, in the ring and/or in the side-chain in cyclic systems. These optionally present double bonds are located between two adjacent C-atoms which are bound to other atoms solely by single bonds.

A primary C-atom in the sense of the above definition is present in the group CH a secondary C-atom in the group --CH The new terpenoids of general formula I are distinguished by specific aroma and/or odorant properties, especially by berry, spice and vegetable notes, for example in combination with the underlying terpenoids. They can accordingly be used for the aromatisation of foods and delicacies as well as of drinks or as odorants for the manufacture of odorant compositions such as perfumes, or can be used for perfuming technical products, for example, solid and liquid detergents, synthetic washing agents, aerosols or cosmetic products of all kinds (e.g. soaps). These compounds can be used in perfumery because of their intensive green notes. The compounds with Z equal to -SH are distinguished by particularly good tenacity. The odorant compositions utilizing these novel compounds, for example perfumed products, can contain a wide proportional range thereof, from 0.005 to 5.0% by weight may be used.

It is to be understood that the scope of the present invention does not include naturally occurring compounds of general formula I.

The novel compounds of formula I can be used in a wide variety of aromatized products. Because of their berry-like aroma properties, these compounds can be used for producing aroma in foods (e.g. milk drinks, yogurt, etc.), in delicacies (e.g. confectionery products such as bonbons, soft ice, etc.) and in drinks (e.g. mineral waters). They can also be used as aroma enhancers for enhancing the aroma of vegetable, soup and snack food aromas where cabbage-like or onion like aromas are especially desired. Their market flavourous qualities make use in small concentration possible. A suitable dosage comprises the range of 0.01 p.p.m. to 100 ppm, preferably of 0.1 p.p.m.1 p.p.m., in the finished product.

The new compounds of general formula I can be obtained in accordance with the invention by reacting a compound of the general formula,

wherein R to R X and Y have the above significance and 11:1 to 3, a double bond represented by X being located in the :,[3-POS1I1OI1 to the carbonyl function or being isomerisable into this position, with a compound HZ (wherein Z signifies the same as above) in the presence of a base under anhydrous conditions, provided that where R and R are hydrogen, R together with R represents a OC- bond, Y is 8 to the carbon atom bearing the substituent R, R where present is hydrogen and R is isopropenyl or isopropylidene, n= 1, then HZ is a lower alkylmercaptan.

As bases there come into consideration, for example: inorganic bases, for example alkali metal hydroxides such as sodium hydroxide or potassium hydroxide, alkaline earth hydroxides such as, for example, calcium hydroxide, organic bases, for example amines such as alkylamines (e.g. diethylamine or triethylamine), heterocyclic amines such as piperidine etc.

By a double bond isomerisable into the 0:,[3-POSitiO1'l to the carbonyl function is meant that double bond in the molecule which is capable under the influence of bases at elevated temperature of migrating into the desired 0a,;3-POSltiOI1 from another position (e.g. li -position).

The reaction of the starting compounds of general formula II in the presence of the said bases is expediently effected in the presence of a solvent. Suitable solvents are, for example, alcohols such as alkanols (e.g. methanol, ethanol, isopropanol, ethanol being preferred), or ethers such as diethyl ether (preferred), or diisopropyl ether.

However, if desired one can also work in the absence of a solvent, especially when the starting material of formula II is brought to reaction with a lower alkylmercaptan. The reaction temperature expediently lies between about 0 C. and 100 (3.; a range between about 40 and 60 C. is preferred. The duration of the reaction depends .on the reaction temperature. For example it amounts to about two hours for a reaction temperature of 40 to 60 C.

The reaction of the present ii1vention can also be initiated by the provision of a free radical initiator, suitably ascaridol or a,a-az0 bis isobutyronitrile.

The reaction can be carried out at normal pressure or expediently at elevated pressure (e.g. 10 atm.), since the reaction proceeds with reduction in volume.

The proportion of the starting compound of general formula II to the sulphur compound HZ can be varied within wide limits; preferably, at least 1 mol of sulphur compound HZ is used per mol of starting compound H. The sulphur compound HZ can, however, also be used in excess.

The reaction of the starting compound II with the sulphur compound HZ is expediently initiated by treating the starting compound II or the solution of this starting compound in an anhydrous solvent with the sulphur compound HZ in the presence of a base (which can be added as such or dissolved in one of the above-named solvents) at a temperature below the boiling point of the sulphur compound HZ and heating the mixture to the reaction temperature in a suitable pressure vessel.

New asymmetric centres can result by the reaction of the starting compound II with the sulphur compound HZ, and consequently the reaction product can be obtained in the stereoisomeric forms thereby possible.

The reaction product can be isolated from the reaction mixture according to conventional methods; for example, by distilling off the solvent, if necessary, filtration of elementary sulphur which was formed from the residual mixture and fractional distillation, by which means the product can be separated from unreacted starting compound II.

In the following Examples, the temperatures are stated in degrees centigrade.

EXAMPLE 1 15.2 g. of piperitone are dissolved in 30 ml. of absolute ether and treated with 1.0 g. triethylamine. The solution is cooled to ca. 75. At this temperature, a total of 5 ml. of hydrogen sulphide is condensed in the course of an hour, the solution initially colouring yellow and later depositing a red-yellow precipitate. After completed .H s-condensation, the reaction product is rapidly transferred into an autoclave, rinsed with 50 ml. of absolute ether and allowed to stand for 29 hours. The pressure rise during the gradual heating to room temperature is very slight, so that a pressure-resistance of the apparatus of 10 atm. is sufiicient. The solution is thereupon filtered and concentrated. The residue (16.9 g.) is fractionally distilled in vacuum. After removal of 7.8 g. of unreacted piperitone there are thus obtained 1.6 g. of p-methane-lthiol-3-one of boiling point 57-59/0.05 mm. Hg, r1 1.4932, in the form of two stereoisomers in the ratio 1:4. (The cis-p-menthane-1-thiol-3-one can be separated from the trans-p-menthane-1-thiol-3-one gas-chromatographically.)

Odour of the product: sulphurous, minty, reminiscent of rhubarb, but also suitable for cassis and blackberry notes.

EXAMPLE 2 15 g. of carvone are treated with a solution of 1 g. of KOH in ml. of absolute ethanol. H 8 is condensed into the solution, cooled to -75, until ca. 20 ml. of H 8 are condensed. After standing overnight in an autoclave at room temperature, the mixture is heated to 50 for 2 hours (in so doing, the pressure rises to 8.5 atm.), then cooled, taken up in ether, the ethereal solution washed with saturated NaCl solution, dried and concentrated. The residue (14.3 g.) is fractionally distilled in vacuum. The distillate (6.3 g.) of boiling point 77-7 8, n 1.5248 to 1.5229, contains, besides ca. 10% of unreacted starting material, a mixture of stereoisomeric p-menth-8-ene-6- thiol-2-ones in the ratio of ca. 1:1: 1.

Odour: Green with sulphurous note, reminiscent of thyme and roast onions.

EXAMPLE 3 15.2 g. of citral (mixture of geranial and neral) are dissolved in 50 ml. of absolute ether and treated with 1 g. of triethylamine. The mixture is cooled to 70 and 10 ml. of hydrogen sulphide are condensed in. After decanting into a pressure vessel, the reaction mixture is allowed to stand overnight at room temperature and then it is heated to 50 for 2 hours. After cooling and removal of the ether, in the residue, only a little citral can still be detected besides the reaction product obtained.

15.2 g. of pulegone are treated with 0.5 ml. of triethylamine and cooled to ca. by means of an ice-common salt mixture. With stirring, methyl mercaptan in excess is condensed into the mixture and, after condensation of 200% of the calculated amount, the mixture is transferred into an autoclave. After standing overnight at room temperature, the reaction mixture is heated to 50 and, after cooling of the autoclave, the reaction product immediately distilled in vacuum. 9.8 g. of 8-methylthio-pmenthan-3-one are obtained as a clear liquid with pleasant odour reminiscent of peppermint, geranium and caraway, boiling point 72-73/0.15 mm. Hg, n 1.4982. The yield amounts to 73% of the theory based on reacted pulegone. The two stereoisomeric compounds 8-methylthio-cis-p-menthan 3 one and 8 methylthio-trans-pmethane-3-one obtained can be separated gas-chromatographically.

EXAMPLE 5 15.2 g. of piperitone and 0.5 g. of triethylamine are cooled to -5. 15 ml. of methyl mercaptan are condensed in with stirring. The mixture is treated and worked up as in Example 4. By fractional distillation, unreacted piperitone is distilled off from the reaction mixture, and the 1-methylthio-p-menthan-3-one enriched to 95% content (boiling point 88/0.1 mm. Hg, n 1.4990). The yield amounts to 6.2 g. or 48% of the theory, based on reacted piperitone. The odour of the product is reminiscent of dill and caraway as well as of boiled white cabbage.

EXAMPLE 6 15.0 g. of carvone are mixed with 0.5 g. of triethylamine. 20 ml. of methyl mercaptan are condensed in this mixture at room temperature. After standing overnight in the autoclave, the mixture is heated to 50 C. for a further 2 hours. After removal of the excess methyl mercaptan, the reaction product is fractionally distilled in vacuum. After a small fore-run of unreacted carvone, there are obtained 14.9 g. of 6-methylthio-p-menth-8-en- 2-one in the form of a mixture of two isomers in the ratio 1:4 (boiling point 105l07/0.2 mm. Hg, 11 1.5067), corresponding to a yield of 78% of the theory. The odour of the mixture is reminiscent of boiled white cabbage with a caraway and onion peel note.

EXAMPLE 7 15 g. of citral and 0.5 of triethylamine are treated with methyl mercaptan as described in Example 6. After removal of the excess of methyl mercaptan, there is obtained a practically citral-free crude product (16 g.) which after distillation yields, besides a polymeric residue, 10.4 g. of 3,7 dimethyl 3 methylthio 6 octenal, corresponding to a yield of 52% of the theory (boiling point 82-84/0.2 mm. Hg, 22 1.4961). The odour of the compound is reminiscent of kohlrabi and cauliflower with a slight citral note.

EXAMPLE 8 Into a suitable autoclave there are charged 9.0 g. of 3-caren-2-one, 0.3 g. of triethylamine and 4 drops of ascaridol. The autoclave is cooled to --20 and 10 ml. of methylmercaptan distilled thereinto. The autoclave is sealed, permitted to stand overnight at room temperature and subsequently warmed to 50 C. for 2 hours. The reaction mixture is fractionally distilled to yield 4-methylthio-2-carone (2.8 g.) in the form of 2 stereoisomers having a boiling point of 80-85 C. at 0.1 mm., 11 1.5210.

The odor of the compound is green and earthy. The resulting aroma is vegetable like and is also reminiscent of the aroma of the tonka bean.

6 EXAMPLE 9 In accordance with the procedure of Example 7 verbenol is reacted with methylmercaptan to yield l-methylthioverbanone, boiling point 70 at 0.1 mm. Hg, n =L5080 (product of 70% purity).

EXAMPLE 10 In accordance with the procedure of example 7 myrtanal is reacted with methylmercaptan to yield 2-methylthiomyrtanal, boiling point 76 at 0.3 mm. Hg, n -=1.5l70. This product contains as an impurity 10% of a by-product. The aroma of the product is leek-like and is reminiscent of cabbages and onions. The undertone is wood and green.

EXAMPLE 11 In accordance with the procedure of Example 8 car-3- en-S-one is reacted with methylmercaptan by heating the reaction mixture in a suitable pressure-vessel for 3 hours to yield 3-methylthio-caran-5one, boiling point ca. 70 at 0.5 mm. Hg, n =1.5224.

The odor of the compound is reminiscent of garlic and shallots and has a fainter smell of rhubarb and vegetables. As side notes of the aroma the aroma of balsam, spices and smoke can also be smelt.

EXAMPLE 12 Odorant composition having a lavender note Parts by weight 6-Mercapto-p-menth-8-en-2-one 10% (in PDE) 50 Spanish wood oil 100 Lavender oil Mont Blanc 450 Linalyl acetate 200 Linalool 50 p-Tert-Butyl-cyclohexyl-acetate 50 Coumarin 5 Cinnamyl alcohol synth. 25 Undecylenaldehyde 10% (in PDE) 5 Terpineol 25 Benzyl alcohol 1,1,4,4,-Tetramethyl 6 ethyl 7 acetyl-l,2,3,4-

tetrahydronaphthalene 5 PDE=diethylphthalate.

The added G-mercapto-p-menth-8-en-2-one enhanced the diffusion and strengthened the floral impression of the composition.

The G-mercapto-p-menth-8-en-2-one added as a solution of its crystalline adduct considerably enhanced the diffusion and rounded the bouquet off.

7 EXAMPLE 14 Aromatisation of a powdered soup A neutral testing powdered soup preparation was prepared according to the following recipe.

Percent NaCl 18 Sugar 12 Sodium glutamate 10 Hydrolyzed vegetable proteins 10 Corn starch 50 For the preparation of 1 liter neutral-testing soup 45 g. of this preparation are necessary. The addition of 2.7- 3.5 g. 6-methylthio-p-menth-8-en-2-one per 100 l. of soup imparted to the neutral-testing soup a pleasant onion and leek-taste.

EXAMPLE 15 Aromatisation of mashed potatoes Neutral testing mashed potatoes are prepared by mixing of 15 g. potato flakes and 85 g. water.

References Cited UNITED STATES PATENTS 2,034,665 3/1936 Ott 26017 2,076,875 4/1937 Borglin et a1. 26016 2,212,150 8/1940 Burke 260593 2,052,210 8/1936 Borglin et al 26016 OTHER REFERENCES Jones et al., J. A. C. S., 60, 2452-55 (1938).

LEON ZITVER, Primary Examiner N. MORGENSTERN, Assistant Examiner US. Cl. X.R. 

